Distinct expression patterns in hepatitis B virus- and hepatitis C virus-infected hepatocellular carcinoma.
OBJECTIVE
To identify biomarkers indicating virus-specific hepatocarcinogenic process, differential mRNA expression in 32 patients with hepatitis B virus (HBV)-/hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) were investigated by means of cDNA microarrays comprising of 886 genes.


METHODS
Thirty two HCC patients were divided into two groups based on viral markers: hepatitis B virus positive and HCV positive. The expression profiles of 32 pairs of specimens (tumorous and surrounding non-tumorous liver tissues), consisting of 886 genes were analyzed.


RESULTS
Seven up-regulated genes in HBV-associated HCC comprised genes involved in protein synthesis (RPS5), cytoskeletal organization (KRT8), apoptosis related genes (CFLAR), transport (ATP5F1), cell membrane receptor related genes (IGFBP2), signal transduction or transcription related genes (MAP3K5), and metastasis-related genes (MMP9). The up-regulated genes in HCV-infected group included 4 genes: VIM (cell structure), ACTB (cell structure), GAPD (glycolysis) and CD58 (cell adhesion). The expression patterns of the 11 genes, identified by cDNA microarray, were confirmed by quantitative RT-PCR in 32 specimens.


CONCLUSIONS
The patterns of all identified genes were classified based on the viral factor involved in HBV- and HCV-associated HCC. Our results strongly suggest that the pattern of gene expression in HCC is closely associated with the etiologic factor. The present study indicates that HBV and HCV cause hepatocarcinogenesis by different mechanisms, and provide novel tools for the diagnosis and treatment of HBV- and HCV-associated HCC.
Lee
Chun-Feng
CF
Institute of Molecular Medicine, National Tsing Hua University, Taiwan 30013, China.
Ling
Zhi-Qiang
ZQ
Zhao
Ting
T
Lee
Kuan-Rong
KR
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D018968:CD58 Antigens / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D016174:Hepacivirus; D006515:Hepatitis B virus; D006801:Humans; D053533:Keratin-8 / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D018968:CD58 Antigens; C506386:CFLAR protein, human; C426203:KRT8 protein, human; D053533:Keratin-8; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C030831:ribosomal protein S5; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases